Sepsis biomarkers in unselected patients on admission to intensive or high-dependency care

Although many sepsis biomarkers have shown promise in selected patient groups, only C-reactive protein and procalcitonin (PCT) have entered clinical practice. The aim of this study was to evaluate three promising novel sepsis biomarkers in unselected patients at admission to intensive care. We assessed the performance of pancreatic stone protein (PSP), soluble CD25 (sCD25) and heparin binding protein (HBP) in distinguishing patients with sepsis from those with a non-infective systemic inflammatory response and the ability of these markers to indicate severity of illness. METHODS: Plasma levels of the biomarkers, PCT and selected inflammatory cytokines were measured in samples taken from 219 patients during the first six hours of admission to intensive or high dependency care. Patients with a systemic inflammatory response were categorized as having sepsis or a non-infective aetiology, with or without markers of severity, using standard diagnostic criteria. RESULTS: Both PSP and sCD25 performed well as biomarkers of sepsis irrespective of severity of illness. For both markers the area under the receiver operating curve (AUC) was greater than 0.9; PSP 0.927 (0.887 to 0.968) and sCD25 0.902 (0.854 to 0.949). Procalcitonin and IL6 also performed well as markers of sepsis whilst in this intensive care unit (ICU) population, HBP did not: PCT 0.840 (0.778 to 0.901), IL6 0.805 (0.739 to 0.870) and HBP 0.607 (0.519 to 0.694). Levels of both PSP and PCT reflected severity of illness and both markers performed well in differentiating patients with severe sepsis from severely ill patients with a non-infective systemic inflammatory response: AUCs 0.955 (0.909 to 1) and 0.837 (0.732 to 0.941) respectively. Although levels of sCD25 did not correlate with severity, the addition of sCD25 to either PCT or PSP in a multivariate model improved the diagnostic accuracy of either marker alone. CONCLUSIONS: PSP and sCD25 perform well as sepsis biomarkers in patients with suspected sepsis at the time of admission to intensive or high dependency care. These markers warrant further assessment of their prognostic value. Whereas previously published data indicate HBP has clinical utility in the emergency department, it did not perform well in an intensive-care population

Historical trends of PBDEs and HBCDs in sediment cores from Sydney estuary, Australia

This paper presents the first historical data on the occurrence of polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCDs) in estuarine sediment from Australia. Sediment cores and surficial sediment samples were collected from four locations within Sydney estuary, Australia. Large increases in concentrations were observed for all compounds between 1980 and 2014, especially for BDE-209 (representative usage of Deca-BDE commercial mixture), which was found in surficial sediment at an average concentration of 42 ng/g thy wt (21-65 ng/g dry wt). PBDE congeners representative of both the Penta- and Octa-BDE commercial mixtures (Sigma 6PBDEs) were also found in their highest concentrations in surficial sediments (average: 1.3 ng/g dry wt; range: 0.65-2.5 ng/g dry wt). PBDE concentrations in surficial sediments were relatively high when compared with those presented in the available literature. This suggests that their input into the Sydney estuary has not decreased since their bans almost a decade earlier. After a sharp increase in the 1990s, HBCD concentrations peaked at an average of 3.5 ng/g dry wt (1.8-53 ng/g dry wt) in surficial samples. With global legislation on HBCDs allowing its usage for the next 10 years, it is expected that its input into the estuary is likely to continue. (C) 2015 Elsevier B.V. All rights reserved

A pitfall in the reconstruction of fibre ODFs using spherical deconvolution of diffusion MRI data

Diffusion weighted ( DW ) MRI facilitates non-invasive quantification of tissue microstructure and, in combination with appropriate signal processing, three-dimensional estimates of fibrous orientation. In recent years, attention has shifted from the diffusion tensor model, which assumes a unimodal Gaussian diffusion displacement profile to recover fibre orientation ( with various well-documented limitations ), towards more complex high angular resolution diffusion imaging ( HARDI ) analysis techniques. Spherical deconvolution ( SD ) approaches assume that the fibre orientation density function ( fODF ) within a voxel can be obtained by deconvolving a ‘common’ single fibre response function from the observed set of DW signals. In practice, this common response function is not known a priori and thus an estimated fibre response must be used. Here the establishment of this single-fibre response function is referred to as ‘calibration’. This work examines the vulnerability of two different SD approaches to inappropriate response function calibration: ( 1 ) constrained spherical harmonic deconvolution ( CSHD )—a technique that exploits spherical harmonic basis sets and ( 2 ) damped Richardson–Lucy ( dRL ) deconvolution—a technique based on the standard Richardson–Lucy deconvolution. Through simulations, the impact of a discrepancy between the calibrated diffusion profiles and the observed ( ‘Target’ ) DW-signals in both single and crossing-fibre configurations was investigated. The results show that CSHD produces spurious fODF peaks ( consistent with well known ringing artefacts ) as the discrepancy between calibration and target response increases, while dRL demonstrates a lower over-all sensitivity to miscalibration ( with a calibration response function for a highly anisotropic fibre being optimal ). However, dRL demonstrates a reduced ability to resolve low anisotropy crossing-fibres compared to CSHD. It is concluded that the range and spatial-distribution of expected single-fibre anisotropies within an image must be carefully considered to ensure selection of the appropriate algorithm, parameters and calibration. Failure to choose the calibration response function carefully may severely impact the quality of any resultant tractography

Association between Organochlorine Pesticides and Vitamin D in Female Subjects

In human population studies, organochlorine pesticides (OCPs) have been linked to vitamin D deficiency. Therefore, this study examined the association between OCPs, vitamin D3 (cholecalciferol, 25(OH)D3), and the active metabolite 1,25-dihydrovitamin D3 (1,25(OH)2D3) in a cohort of non-obese women. The serum samples of 58 female participants (age—31.9 ± 4.6 years; body mass index (BMI)—25.7 ± 3.7 kg/m2) were screened for 10 indicator OCPs. 25(OH)D3 and 1,25(OH)2D3 levels were determined via isotope dilution liquid chromatography tandem mass spectrometry. In this cohort, the 25(OH)D3 and 1,25(OH)2D3 levels were 22.9 ± 11.2 ng/mL and 0.05 ± 0.02 ng/mL, respectively, with 28 participants classified as 25(OH)D3-deficient (<50 nmol/L). In the study cohort, no correlations were found between individual or total OCPs (ƩOCPs) and 25(OH)D3. p,p′-dichlorodiphenyldichloroethylene (DDE) and ƩOCPs correlated positively with 1,25(OH)2D3, with the latter being negatively correlated with estimated glomerular filtration rate (eGFR). In women with sufficient 25(OH)D3 levels, p,p′-dichlorodiphenyltrichloroethan (DDT) was positively correlated with 1,25(OH)2D3, whilst in the deficient group, hexachlorobenzene (HCB) and p,p′-(DDE) were positively correlated with 1,25(OH)2D3, β-Hexachlorocyclohexane (HCH) was positively correlated with 25(OH)D3, and none of the OCPs were associated with measures of renal function. Overall, OCPs and ƩOCPs were not associated with 25(OH)D3, suggesting that they are unrelated to vitamin D deficiency, but p,p′-DDE and ƩOCPs correlated positively with active 1,25(OH)2D3, while ƩOCPs correlated negatively with eGFR, suggesting a possible renal effect. Analysis of vitamin D deficiency revealed an association between β-HCH and 25(OH)D3, and between HCB and p,p′-DDE and 1,25(OH)2D3, suggesting that OCP effects may be enhanced in cases of vitamin D deficiency

Serum measures of hexabromocyclododecane (HBCDD) and polyborminated diphenyl ethers (PBDEs) in reproductive-aged women in the United Kingdom

We investigated the serum concentrations of two brominated flame retardants (BFRs) – polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCDD) –in 59 women aged between 23 and 42 from the United Kingdom. We also collected demographic data, including age, bodyweight and height in order to test for associations with BFR levels. Temporal and global differences were also assessed using previously published data.HBCDD was detected in 68% of samples with a mean concentration of 2.2 ng/g lipid (range =< 0.3–13 ng/g lipid). The dominant stereoisomer was α-HBCDD with an average contribution of 82% (0–100%) towards ΣHBCDD, was followed by γ-HBCDD (average contribution = 17%). PBDEs were detected in 95% of samples with a mean ∑PBDE (sum of BDEs −28, −47, −99, −100, −153, −154 and −183) concentration of 2.4 ng/g lipid (range = 2.5 since 2010. Whilst the human body burden appear to be decreasing, both PBDEs and HBCDD are still consistently detected in human serum, despite legislative action limiting their production and use. This highlights the need to continuously assess human exposure and the effectiveness of policy aimed at reducing exposure

Serum polychlorinated biphenyl levels and circulating miRNAs in non-obese women with and without polycystic ovary syndrome

IntroductionPolychlorinated biphenyls (PCBs), organic lipophilic pollutants that accumulate through diet and increase with age, have been associated with polycystic ovary syndrome (PCOS) and shown to affect microRNA (miRNA) expression. This work aimed to determine if PCBs were associated with circulating miRNAs and whether there were any correlations with serum PCB/miRNA levels and hormonal changes.Methods29 non-obese PCOS and 29 healthy control women, with similar age and body mass index (BMI), had their serum miRNAs measured together with 7 indicator PCBs (PCB28, PCB52, PCB101, PCB118, PCB138, PCB153, PCB180) using high resolution gas chromatography coupled with high resolution mass spectrometry.ResultsIn the combined study cohort, four miRNAs (hsa-miR-139-5p, hsa-miR-424-5p, hsa-miR-195-5p, hsa-miR-335-5p) correlated with PCBs, but none correlated with metabolic parameters. hsa-miR-335-5p correlated with FSH. When stratified, 25 miRNAs correlated with PCBs in controls compared to only one (hsa-miR-193a-5p) in PCOS; none of these miRNAs correlated with the metabolic parameters of BMI, insulin resistance, or inflammation (C-reactive protein, CRP). However, of these 25 miRNAs in controls, hsa-miR-26a-5p, hsa-miR-193a-5p, hsa-miR-2110 and hsa-miR-195-5p positively correlated with luteinizing hormone (LH), hsa-miR-99b-5p and hsa-miR-146b-5p correlated with estradiol, hsa-miR-193a-5p correlated with progesterone, hsa-miR-195-5p correlated with follicle stimulating hormone (FSH), and hsa-miR-139-5p and hsa-miR-146b-5p negatively correlated with anti-müllerian hormone (AMH) (all p&lt;0.05). hsa-miR-193a-5p in PCOS cases correlated with estradiol.ConclusionIn this cohort of women, with no difference in age and BMI, and with similar PCB levels, the miRNAs correlating to PCBs associated with menstrual cycle factors in healthy menstruating controls versus the anovulatory PCOS subjects. The PCB-associated miRNAs did not correlate with non-reproductive hormonal and metabolic parameters. This suggests that PCB effects on miRNAs may result in changes to the hypothalamo-ovarian axis that may thus affect fertility

Mapping spatial dimensions of Wilderness recreation outcomes: a study of overnight users

Grand Teton National Park (GRTE) is a popular mountain recreation destination which, like many National Park Service (NPS) units, has experienced a significant increase in visitation in recent years, with total visits increasing by 27% between 2014 and 2017 (NPS 2020). Particularly popular within GRTE is the String and Leigh Lakes (SLL) area, which is a favoured alpine destination for numerous day-use recreation activities and also an important starting point for backcountry and overnight recreational users within GRTE’s Recommended Wilderness. To better understand the visitor experience of overnight backcountry recreationists in the SLL area, data were collected using novel public participatory geographic information systems (PPGIS) during the summer of 2018. PPGIS data were used to identify the locations in which overnight recreationists experienced positive and negative recreation outcomes. Results indicate that they experience more positive outcomes within the Recommended Wilderness, away from high-density, trailhead-proximate areas outside the Recommended Wilderness. Findings also indicate that overnight users experience crowding and conflict more outside of the Recommended Wilderness than elsewhere on their backcountry trip. While this may seem intuitive, these are some of the first empirical results spatially contextualizing backcountry visitor outcomes in a popular national park. The findings thus provide managers with a visitor experience baseline that can be monitored and adaptively managed in the future

Detailing patient specific modelling to aid clinical decision-making

The anatomy of the craniofacial skeleton has been described through the aid of dissection identifying hard and soft tissue structures. Although the macro and microscopic investigation of internal facial tissues have provided invaluable information on constitution of the tissues it is important to inspect and model facial tissues in the living individual. Detailing the form and function of facial tissues will be invaluable in clinical diagnoses and planned corrective surgical interventions such as management of facial palsies and craniofacial disharmony/anomalies. Recent advances in lower-cost, non-invasive imaging and computing power (surface scanning, Cone Beam Computerized Tomography (CBCT) and Magnetic Resonance (MRI)) has enabled the ability to capture and process surface and internal structures to a high resolution. The three-dimensional surface facial capture has enabled characterization of facial features all of which will influence subtleties in facial movement and surgical planning. This chapter will describe the factors that influence facial morphology in terms of gender and age differences, facial movement—surface and underlying structures, modeling based on average structures, orientation of facial muscle fibers, biomechanics of movement—proof of principle and surgical intervention

Investigation of the association of Apgar score with maternal socio-economic and biological factors: an analysis of German perinatal statistics

PURPOSE: To examine the relationship of 5-min Apgar score with maternal socio-economic and biological factors. METHODS: We analyzed data from 465,964 singleton pregnancies (37–41 weeks’ gestation) from the German perinatal statistics of 1998–2000. Using a logistic regression model we analyzed the incidence of low (0–6) 5-min Apgar scores in relation to these maternal factors: body mass index (BMI), age, previous live births, country of origin, occupation, single mother status, working during pregnancy, and smoking. RESULTS: A low Apgar score was more common in overweight [adjusted odds ratio (OR) 1.24; 95% confidence interval (CI) 1.10–1.40; P &lt; 0.001] and obese [OR 1.92 (95% CI 1.67–2.20); P &lt; 0.001] compared to normal weight women. A low Apgar score was also more common for women aged &gt;35 years compared to those aged 20–35 years [OR 1.35 (95% CI 1.16–1.58); P &lt; 0.001]. Furthermore, odds of a low Apgar score were higher for women with no previous live births compared to those with one or more previous live births [OR 1.52 (95% CI 1.37–1.70); P &lt; 0.001]. Socio-economic factors did not convincingly influence Apgar scores. CONCLUSIONS: There was an influence of the biological maternal factors age, BMI, and parity on the 5-min Apgar score. There was no convincing effect of socio-economic factors on Apgar score in our study population. Possible reasons for this are discussed